3,3‘-Disubstituted BINAP Ligands:  Synthesis, Resolution, and Applications in Asymmetric Hydrogenation

Abstract

A novel family of BINAP ligands were prepared with alkoxy-and acetoxy-derived substituents in the 3,3′-positions. They were prepared through a convergent synthesis starting from readily available 4-bromo-2-naphthol. These ligands afforded excellent enantioselectivities in the asymmetric hydrogenation of substituted olefins. The presence of the 3,3′-substituents was shown to be beneficial by a direct comparison with the parent unsubstituted BINAP.

Iridium‐Catalysed Asymmetric Hydrogenation of Enamides in the Presence of 3,3′‐Substituted H8‐Phosphoramidites

“…Notably, a beneficial effect of the 3,3'-disubstitution on enantioselectivity has also been reported with BINAP ligands in the asymmetric hydrogenation of N-(1-phenylvinyl)acetamide. [12] From the results shown, it was not clear whether the active system was still a monodentate iridiumphosphoramidite complex. However, reactions with two equivalents of ligand did not show any increase in enantioselectivity.…”

Synthesis and resolution of the biaryl-like diphosphine (S)-Me2-CATPHOS, preparation of a derived rhodium precatalyst and applications in asymmetric hydrogenation

“…However, even though 1 has attained this privileged status and is an excellent ligand for a host of transition metal-catalyzed transformations, it is not superior for all transformations and is often substrate specific 4 ; in such cases, it is necessary to modify the electronic and/or steric properties to optimize performance, and this can involve nontrivial multistep de novo syntheses 3 . For example, the dramatic dependence of the biaryl architecture on catalyst performance has been reported for the rhodium-catalyzed asymmetric hydrogenation of dehydroamino acids [19][20][21] ; although cationic Rh/(S)-1 was a poor catalyst for the asymmetric hydrogenation of 2-acetamidoacrylic acid derivatives, yielding an ee as low as 14%, the use of 3,3′-disubstituted 1 resulted in a marked enhancement in enantioselectivity, with ee values reaching 99%. However, this enhancement was restricted to unhindered alkenes, as more hindered substrates gave low enantioselectivities, emphasizing the substrate-specific nature of the catalyst and the need for further modification/elaboration.…”

A new route to 2,2′,3,3′-tetrasubstituted binaphthyls

“…7 More difficult is the preparation of binaphthyls with 2,2 0 -substituents other than OR, since this requires either (a) a stereoconservative exchange of two OR, both di-ortho substituted; which may be difficult from steric reasons and reduced racemization barrier of intermediates, 8 (b) the use of other ortho-directing groups, 9 (c) a diastereoselective binaphthyl coupling of suitable substituted naphthalene precursors or (d) an optical resolution step of the final product. 10 Examples for the first route have been published by Maruoka's group to obtain tetrasubstituted binaphthyls with carbon substituents in pos. 2, 2 0 , 3, and 3 0 from binaphthol (7-10 steps, 50-65% overall yield).…”